Darvon, Darvocet Withdrawn in U.S. Over Heart Risks

Nov. 19 (Bloomberg) -- Darvon, a 53-year-old pain pill,
will be pulled from the U.S. market after a study found
potentially fatal heart risks in healthy people who take the
medicine at the recommended dose.

Xanodyne Pharmaceuticals Inc., the drug’s owner since 2005,
will withdraw Darvon and Darvocet, a product that combines
Darvon’s active ingredient with acetaminophen, Food and Drug
Administration officials said today in a statement. The agency
requested the move after evaluating study data, and asked makers
of generic versions to take them off the market as well.
Darvon’s active ingredient, the opioid propoxyphene, had been
approved in 1957 for treating mild to moderate pain.

The U.K. announced in 2005 that it would pull propoxyphene-containing drugs from the market, citing reports of as many of
400 fatal overdoses a year. The European Medicines Agency
recommended a ban last year. Also last year, the FDA rejected an
advisory panel’s recommendation to withdraw the drug, opting
instead to require a new safety study and a black-box warning
label about the risks of excessive use.

Xanodyne’s new clinical research, combined with new
epidemiological data, led the FDA to conclude that
propoxyphene’s benefits no longer outweigh its risks, said John
Jenkins, director of the agency’s Office of New Drugs.

All Users at Risk

The data “suggested that the heart risk of propoxyphene
could apply to all users, not just those who took excessive
doses or those with medical conditions,” such as reduced kidney
function, Jenkins said today during a conference call.

Xanodyne, a closely held drugmaker in Newport, Kentucky,
that doesn’t disclose sales figures, acquired Darvon and
Darvocet in July 2005 from a company that had bought the rights
from Indianapolis-based Eli Lilly & Co., the developer of the
medicines.

Xanodyne removed the drug as “part of a market-wide
withdrawal applying to all propoxyphene-containing products,
affecting branded and generic pharmaceutical companies,” the
company said today in a statement. Darvon and Darvocet represent
less than 1 percent of the propoxyphene market in total
prescriptions, Natasha Giordano, Xanodyne’s chief executive
officer, said today in a separate e-mail.

Those two brands “have never been promoted in any way by
Xanodyne, neither through personal promotion by sales
representatives nor direct-to-consumer or direct-to-doctor
advertising or promotions,” Giordano said.

U.S. Prescriptions

About 10 million people in the U.S. received prescriptions
for propoxyphene-containing products in 2009, said Gerald Dal
Pan, director of the FDA’s Office of Surveillance and
Epidemiology, on the conference call.

“For the first time, we now have data showing that the
standard therapeutic dose of propoxyphene can be harmful to the
heart,” he said in the statement.

Users of the drug “need to know that these changes to the
heart’s electrical activity are not cumulative,” he said.
“Once patients stop taking propoxyphene, the risk will go
away.”

Public Citizen will ask Congress to investigate why the FDA
didn’t take propoxyphene off the market years ago, said Sidney
Wolfe, the Washington-based consumer group’s director of health
research.

“Evidence going back more than 30 years indicates that
propoxyphene is not very effective, is toxic at doses not much
higher than the recommend dose,” and is “somewhat addictive,”
Wolfe said today in a statement. “Due to FDA negligence, at
least 1,000 to 2,000 or more people in the U.S. have died from
using propoxyphene since the time the U.K. ban was announced”
in 2005, he said.